Predominantly post-transcriptional regulation of activation molecules in chronic lymphocytic leukemia: The case of transferrin receptors.

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Predominantly post-transcriptional regulation of activation molecules in chronic

lymphocytic leukemia: The case of transferrin receptors.

Ioanna Chiotoglou, Tatjana Smilevska, Samara, Sophia Likousi, Chrysoula

Belessi, Ioanna Athanasiadou, Niki Stavroyianni, Stavroula Samara, Nikolaos

Laoutaris, Nikolaos Vamvakopoulos, Achilles Anagnostopoulos, Athanasios Fassas,

Kostas Stamatopoulos, and Panagoula Kollia

Blood Cells Mol Dis, July 11, 2008;

Laboratory of Cytogenetics and Molecular Genetics, School of Medicine,

University of Thessaly, 41222 Larissa, Greece.

Transcriptional and post-transcriptional control mechanisms have a differential

impact on cellular physiology depending on activation status. Several lines of

evidence suggest that chronic lymphocytic leukemia (CLL) malignant B cells

resemble antigen-experienced and activated B cells. In the present study, we

investigated the expression of transferrin receptor 1 (TfR1, CD71), one of the

" classical " markers up-regulated upon B-cell activation, and TfR2, a novel

receptor for transferrin, in peripheral blood CD19(+) B cells from ten healthy

individuals and 76 patients with CLL so as to gain insight into potential

disease-related differences in underlying regulatory mechanisms. Marked

differences in the production and expression of these receptors were detected in

malignant but not in normal B cells. Specifically, TfR1 mRNA and protein levels

were significantly higher in comparison to TfR2, both in normal and malignant B

cells. Furthermore, discrepancies between TfR mRNA and protein expression were

observed in CLL; in contrast, mRNA and protein expression levels were generally

concordant in normal B cells. Exposure to actinomycin D decreased TfR1 and TfR2

mRNA levels in normal CD19(+) B cells but had no effect on CLL malignant cells.

The protein synthesis inhibitor cycloheximide had opposing effects in normal vs.

CLL malignant B cells: thus, TfR1 and TfR2 mRNA levels were increased in normal

B cells, whereas they were unaffected or even suppressed in CLL malignant B

cells. These results allude to differential regulation of TfR1 and TfR2

expression in normal B cells vs. CLL. In normal B cells, transcriptional

mechanisms exert a critical control over TfR1 and TfR2 expression, whereas in

CLL post-transcriptional mechanisms seem to play a complementary and perhaps

more important role. This type of control appears to be especially suited for

modulation of genes implicated in proliferation of activated cells, like CLL

malignant B cells.

PMID: 18621559